Dosage forms.ppt

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Pharmaceutical Dosage

Forms And Delivery

Systems

Dr. Mohammad Shariare

Dr. Mohammad Shariare Assistant Professor

Assistant Professor

North South University

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Introduction

• Active drug substance (active pharmaceutical ingredient - API)

– _{chemical compound with pharmacological (or other direct effect )}

intended for used in diagnosis, treatment or prevention of diseases • Direct clinical use of the active drug substances “as they are” is rare due

to the number of good reasons:

– _{API handling can be difficult or impossible (e.g., low mg and}_{g doses)} – _{Accurate drug dosing can be difficult or impossible}

– API administration can be impractical, unfeasible or not according to the therapeutically aims

– Some API can benefit from reducing the exposure to the environmental factors (light, moisture…), or they need to be chemically stabilised due to the inherent chemical instability

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Introduction

– API may cause local irritations or injury when they are present at high concentrations at the site of administration

– API can have unpleasant organoleptic qualities (taste, smell – compliance!)

– Administration of active substance would mean to have no chance for modification (improvement) of its PK profile

• Besides the choice of the active drug substance, you need to also make a responsible decision regarding the route of administration and the DOSAGE FORM (drug delivery system) – wrong choice can cause failure of therapy.

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From drug substance to

pharmaceutical preparation

• Active drug substance (active pharmaceutical ingredient - API) • Excipients (inactive pharmaceutical ingredients)

– Technological, biopharmaceutical and/or stability reasons

– Diluents/fillers, binders, lubricants, desintegrants, coatings, preservants and stabilizers, colorants and flavourings

– Should always be stated in SPC (important in the case of allergies)

• Pharmaceutical dosage form

– determines the physical form of the final pharmaceutical preparation

– is a drug delivery system which is formed by technological processing (drug formulation) – must reflect therapeutic intentions, route of administrations, dosing etc.

• Pharmaceutical preparation (PP)

– particular pharmaceutical product containing active and inactive pharmaceutical ingredients formulated into the particular dosage form.

– Packed and labelled appropriately

– Two major types of PP according the origin:

• Manufactured in large scales by pharmaceutical industry (original and generic preparations)

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They are classified according to the following:

Dosage Form

Types of dosage forms

Route of administration

Oral Topical

Rectal Parenteral

Vaginal Inhalation Ophthalmic

Otic

Physical form

Solid

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Oral dosage forms

Tablets

• A tablet

is a hard, compressed medication in round, oval

or square shape.

• The excipients include

:

• Binders, glidants (flow aids) and lubricants to ensure

efficient tabletting.

• Disintegrants to ensure that the tablet breaks up in the

digestive tract.

• Sweeteners or flavours to mask the taste of bad-tasting

active ingredients.

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Tablets

– Conventional tablets

• Disintegration/ Desegregation/ Dissolution, can be divided (half/quarters)

– Coated tablets (not to be divided)

• To mask unpleasant taste or smell of API

• To avoid of adhesion in oesophagus (to facilitate swallowing and/or avoid release of API and local adverse reactions)

• To ensure drug stability

• To provide enterosolvent coating

– To overcome – possible degradation of API in the

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Oral dosage forms

Buccal and sublingual tablets

 Sublingual and buccal medications are administered by placing them in the mouth, either under the tongue (sublingual) or between the gum and the cheek (buccal).

 The medications dissolve rapidly and are absorbed through the mucous membranes of the mouth, where they enter into the bloodstream.

 Avoid the acid and enzymatic environment of the stomach and the drug metabolizing enzymes of the liver.

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Oral dosage forms

Effervescent

tablets



Effervescent

tablets

are uncoated tablets that generally

contain acid substances (citric and tartaric acids) and

carbonates or bicarbonates and which react rapidly in the

presence of water by releasing carbon dioxide.



They are intended to be dissolved or dispersed in water

before use providing:

 Very rapid tablet dispersion and dissolution.

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Oral dosage Forms

Chewable tablet



They are tablets that chewed prior to swallowing.

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Oral dosage forms

Capsules

 A capsule is a medication in a gelatin container. It is not intended to be divided and can also be compounded individually.

 In the GIT gelatin shell softens, swells and dissolve – particles are dispersed 

disintegration  API dissolution  absorption - Hygroscopic

- Enteric coating available

 Advantage: mask the unpleasant taste of its contents and quicker action as compared to tablets.

 The two main types of capsules are:

 hard-shelled capsules, which are normally used for dry, powdered ingredients,

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Oral Dosage Forms

Lozenge



It is a solid preparation consisting of sugar and

gum, the latter giving strength and cohesiveness

to the lozenge and facilitating slow release of the

medicament.



_{It is used to medicate the mouth and throat for}

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Oral Dosage Forms

Pastilles



They are solid medicated preparations designed to

dissolve slowly in the mouth. They are softer than

lozenges and their bases are either glycerol and gelatin,

or acacia and sugar.

Dental Cones



A tablet form intended to be placed in the empty socket

following a tooth extraction, for preventing the local

multiplication of pathogenic bacteria associated with

tooth extractions.

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Oral Dosage Forms

Granules

 They are consisting of solid, dry aggregates of powder particles often supplied in single-dose sachets.

 Some granules are placed on the tongue and swallowed with water, others are intended to be dissolved in water before taking.

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Oral Dosage Forms

Powder (Oral)

 There are two kinds of powder intended for internal use.

 Bulk Powders are multidose preparations consisting of solid, loose, dry particles of varying degrees of fineness. They contain one or more active ingredients, with or without excipients and, if necessary, coloring matter and flavoring substances.

 Usually contain non-potent medicaments such as antacids since the patient measures a dose by volume using a 5ml medicine spoon. The powder is then usually dispersed in water or, in the case of effervescent powders, dissolved before taking.

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Oral Dosage Forms

Powders for mixtures

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Oral Dosage Forms

Liquid preparations

 Oral solution

Oral solutions are clear Liquid preparations for oral use containing one or more active ingredients dissolved in a suitable vehicle.

cyclosporine, paracetamol

 Syrup

- It is a concentrated aqueous solution of a sugar, usually sucrose.

- Flavored syrups are a convenient form of masking disagreeable tastes. - chlorpherinamine

 Elixir

- It is pleasantly flavored clear liquid oral preparation of potent or nauseous drugs.

- sweetened hydroalcoholic solution.

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Liquid preparations

Oral emulsion:

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Liquid Preparations

 Oral suspension

- Oral suspensions are Liquid preparations for oral use containing one or more active ingredients suspended in a suitable vehicle.

- Oral suspensions may show a sediment which is readily dispersed on shaking to give a uniform suspension which remains sufficiently stable to enable the correct dose to be delivered.

- Advantages: easier for administration (children, elderly people), good compliance (can be flavoured), rapid absorption, flexible dosing

- Disadvantages: stability (chemical, microbial… - a need for preservatives), accurate dosing???

- should not be used for drugs with high potency (dosing!)

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Liquid preparations

Linctuses

• Linctuses are viscous, liquid oral preparations that are usually prescribed for the relief of cough.

• They usually contain a high proportion of syrup and glycerol which have a demulcent effect (soothing effect) on the membranes of the throat.

• The dose volume is small (5ml) and, to prolong the demulcent action, they should be taken undiluted.

Oral Drops

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Liquid preparations

Gargles

 They are aqueous solutions used in the prevention or treatment of throat infections.

 Usually they are prepared in a concentrated solution with directions for the patient to dilute with warm water before use.

 betadine

Mouthwashes

 These are similar to gargles but are used for oral hygiene and to treat infections of the mouth.

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Topical dosage forms

:

Ointments

• Ointments are semi-solid, greasy preparations

for application to the skin, rectum or nasal

mucosa.

• The base is usually anhydrous and immiscible

with skin secretions.

• Ointments may be used as emollients or to

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Topical dosage forms

Creams

 Creams are semi-solid emulsions, that is mixtures of oil and water.

 _{They are divided into two types:}

A- oil-in-water (O/W) creams: which are composed of small droplets of oil dispersed in a continuous aqueous phase.

Oil-in-water creams are more comfortable and cosmetically acceptable as they are less greasy and more easily washed off using water.

B- water-in-oil (W/O) creams: which are composed of small droplets of water dispersed in a continuous oily phase.

Water-in-oil creams are more difficult to handle but many drugs which are incorporated into creams are hydrophobic and will be released more readily from a water-in-oil cream than an oil-in-water cream.

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Topical dosage forms

Gels (Jellies)

• Gels are semisolid system in which a liquid phase is constrained

within a 3-D polymeric matrix (consisting of natural or synthetic

gum) having a high degree of physical or chemical cross-linking.

• They are used for medication, lubrication and some

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Topical dosage forms

Pastes

 Pastes are basically ointments into which a high percentage of

insoluble solid has been added

 The extraordinary amount of particulate matter stiffens the system.

 Pastes are less penetrating and less macerating and less heating

than ointment.

 Pastes make particularly good protective barrier when placed on

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Topical dosage forms

There are two types of pastes:

a) Fatty pastes

b) Non greasy pastes

Dusting powders

- These are free flowing very fine

powders for external use.

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Topical dosage forms

Liniments

- Liniments are fluid, semi-fluid or, occasionally,

semi-solid preparations intended for application to

the skin.

- They may be alcoholic or oily solutions or

emulsions.

- Most are massaged into the skin (e.g.

counter-irritant).

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Topical dosage forms

Lotions

- These are fluid preparations (aqueous) for

external application without friction.

- They are either dabbed on the skin or applied on

a suitable dressing and covered with a

waterproof dressing to reduce evaporation.

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Topical dosage forms

Transdermal patch

- A transdermal patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream.

- An advantage of a transdermal drug delivery route over other types such as oral, topical, etc is that it provides a controlled release of the medicament into the patient.

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Transdermal drug delivery sytems (TDDS)

• Advantages

– Elegant alternative to injectables • Pain and stress-free

• No need for trained specialist – Good compliance

• Disadvantages

– Not feasible for all API ! • Well balanced lipohilicity

• High potency (high doses can not be accommodated and delivered) – Local relations (irritation, disruption of barrier skin function)

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Implants

• Implants

– Controlled drug delivery for over a long time

(months/years)

– Principle

• Reservoir (Osmotic/diffusion) systems • Matrix systems

– Non-biodegradable

– Biodegrable polymeric materials with dispersed drug

• Advantages – largely overcomes problems with individual

compliance

• Disadvantages – mini-surgery is needed, uneasy to simply

discontinue the therapy, local reactions

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Rectal dosage forms

Suppository

 It is a small solid medicated mass, usually cone-shaped ,that is inserted either into the rectum (rectal suppository), vagina (vaginal suppository or pessaries) where it melts at body temperature.

 Advantages: offers an alternative to p.o. – especially useful when patient can not swallow the drug (unconsciousness, vomiting patents, serious GIT

disturbances. Children) or when we need to avoid local adverse reactions (e.g., NSAIDs).

 Disadvantages: poor compliance, some API can cause local irritation of rectal mucosa, stability of the dosage form during high temp., the melted supp. matter may come out.

 Storage: cool place!

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Rectal dosage forms

Enema



An

enema

is the procedure of introducing liquids into the

rectum and colon via the anus.

Types of enema:

1- Evacuant enema:

used

as a bowel stimulant to treat

constipation. E.g. soft soap enema & Mgso

₄

enema

-The volume of evacuant enemas may reach up to 2 liters.

- They should be warmed to body temperature before

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Vaginal dosage forms

Douche

• A

douche

is a device used to introduce a stream of

water into the body for medical or hygienic reasons.

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Parenteral dosage forms:

Injectables



An

injection

is an infusion method of putting liquid into the

body, usually with a hollow needle and a syringe which is

pierced through the skin to a sufficient depth for the material

to be forced into the body.



Solutions, emulsions or suspensions which MUST BE

– STERILE – free of microorganisms (microbiological tests)

– PYROGEN-FREE (test for pyrogens)

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Parenteral dosage forms

Intravenous injection

 It is a liquid administered directly into the bloodstream via a vein.

 It is advantageous when a rapid onset of action is needed.

 Must be PARTICLE-FREE (visual inspection prior administration!)

 Not intended for API inducing clotting or haemolysis

 Isoacidity is desirable – but different pH often needed to assure solubility of API or chemical stability (may cause local reaction – phlebitis or pain at the site of injection)

 Moderately irritating compounds can be administered (e.g., anticancer drugs)

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Parenteral dosage forms

Intramuscular injection

 It is the injection of a substance directly into a muscle.

 Many vaccines are administered intramuscularly.

 Depending on the chemical properties of the drug, the medication may either be absorbed fairly quickly or more gradually.

Subcutaneous injection

• Subcutaneous injections are given by injecting a fluid into the subcutis, the layer of skin directly below the dermis and epidermis. • Subcutaneous injections are highly effective in administering

vaccines and such medications as insulin. • For both IM and SC:

 Isoacidity should be guaranteed (to avoid risk of inflammation/necrosis of the tissues)

 API and excipients should be non-irritating

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Inhaled dosage forms:

Inhaler

- Inhalers are solutions, suspensions or emulsion of drugs in a mixture of inert propellants held under pressure in an aerosol dispenser.

- Release of a dose of the medicament in the form of droplets of 50 um diameter or less from the container through a spring-loaded valve incorporating a metering device. The patient then inhales the released drug through a mouthpiece.

- In some types, the valve is actuated by finger pressure, in other types the valve is actuated by the patient breathing in through the mouthpiece.

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Inhaled dosage forms

Nebulizer or (atomizer)

• A nebulizer is a device used to administer medication to people in forms of a liquid mist to the airways.

•

• It is commonly used in treating asthma, and other respiratory diseases.

• It pumps air or oxygen through a liquid medicine to turn it into a vapor, which is then inhaled by the patient.

• As a general rule, doctors generally prefer to prescribe inhalers for their patients, because:

– These are cheaper – more portable

– carry less risk of side effects.

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Ophthalmic dosage forms:

Eye drops

• Eye drops are saline-containing drops used as a vehicle to administer medication in the eye.

•

• Depending on the condition being treated, they may contain steroids, antihistamines or topical anesthetics.

• Eye drops sometimes do not have medications in them and are only lubricating and tear-replacing solutions.